The CCR4-NOT complex is a tumor suppressor in Drosophila melanogaster eye cancer models View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Carmen Vicente, Rocco Stirparo, Sofie Demeyer, Charles E. de Bock, Olga Gielen, Mardelle Atkins, Jiekun Yan, Georg Halder, Bassem A. Hassan, Jan Cools

ABSTRACT

BACKGROUND: The CNOT3 protein is a subunit of the CCR4-NOT complex, which is involved in mRNA degradation. We recently identified CNOT3 loss-of-function mutations in patients with T-cell acute lymphoblastic leukemia (T-ALL). METHODS: Here, we use different Drosophila melanogaster eye cancer models to study the potential tumor suppressor function of Not3, the CNOT3 orthologue, and other members of the CCR4-NOT complex. RESULTS: Our data show that knockdown of Not3, the structural components Not1/Not2, and the deadenylases twin/Pop2 all result in increased tumor formation. In addition, overexpression of Not3 could reduce tumor formation. Not3 downregulation has a mild but broad effect on gene expression and leads to increased levels of genes involved in DNA replication and ribosome biogenesis. CycB upregulation also contributes to the Not3 tumor phenotype. Similar findings were obtained in human T-ALL cell lines, pointing out the conserved function of Not3. CONCLUSIONS: Together, our data establish a critical role for Not3 and the entire CCR4-NOT complex as tumor suppressor. More... »

PAGES

108

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s13045-018-0650-0

    DOI

    http://dx.doi.org/10.1186/s13045-018-0650-0

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1106341818

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30144809


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